Aerobic exercise increases hippocampal volume in older women with probable mild cognitive impairment: a 6-month randomised controlled trial

This study investigated the effects of two types of exercise training on brain structure (specifically, hippocampal volume) and its association with verbal memory and learning in older women with probable mild cognitive impairment (MCI).

The interventions tested were:

• Aerobic Training (AT): Exercise designed to improve cardiovascular fitness, such as brisk walking or cycling.
• Resistance Training (RT): Exercise focused on increasing muscle mass, strength, and power, typically involving weights or resistance machines.

The comparator group received:

• Balance and Tone Training (BAT): A control intervention consisting of balance and toning exercises, which served as a non-aerobic and non-resistance exercise control.

The primary outcome measure for this specific analysis was:

• Hippocampal Volume: The size of the hippocampus, a brain region critical for memory and learning, measured separately for the left, right, and total hippocampus.

Secondary outcome measures included:

• Verbal Memory and Learning: Assessed using a standardized neuropsychological test.
• Association between changes in hippocampal volume and changes in verbal memory performance.

The study included 86 females who were 70 to 80 years old and living independently in their own homes in Vancouver, Canada. All participants had probable Mild Cognitive Impairment (MCI), which means they experienced cognitive decline greater than expected for their age and education, but it did not significantly interfere with their daily function. MCI is a known risk factor for dementia.

Specific criteria for inclusion were:

• Aged 70 to 80 years.
• Living independently.
• Scored ≥ 24 out of 30 on the Mini-Mental State Examination (MMSE), indicating general cognitive function.
• Scored < 26 out of 30 on the Montreal Cognitive Assessment (MoCA), which is more sensitive to subtle cognitive impairments than the MMSE.
• Answered "yes" to the question "Do you have any difficulty with your memory?".
• Scored ≥ 6 out of 8 on the Lawton and Brody Instrumental Activities of Daily Living (IADL) scale, indicating preserved ability to perform complex daily tasks.
• Had a visual acuity of at least 20/40 (with or without corrective lenses).
• Obtained physician's clearance to start a supervised exercise program.

Participants were excluded if they:

• Had a current medical condition for which exercise was contraindicated.
• Had regularly participated in resistance training or aerobic training in the last six months.
• Had a neurodegenerative disease (like Parkinson's) or a history of stroke.
• Had a diagnosed psychiatric condition (e.g., depression).
• Had a diagnosis of dementia of any type.
• Did not speak and understand English fluently.
• Were on estrogen replacement therapy.

The study focused exclusively on women due to potential sex differences in how the brain responds to exercise.

The researchers used several instruments and scales to assess participants' cognitive status, physical activity, and brain structure:

1. Hippocampal Volume (Primary Outcome):

• Magnetic Resonance Imaging (MRI): A 3T Philips Achieva MRI scanner was used to acquire structural T1-weighted images of the brain at baseline and after 6 months. This advanced imaging technique provides detailed pictures of brain structures.
• FIRST (FMRIB Software Library): The T1-weighted images were analyzed using FIRST, a sophisticated, model-based segmentation and registration tool. This software uses pre-defined models of brain structures (constructed from 317 manually-segmented images) to automatically identify and calculate the volume of the left and right hippocampi.
• Manual Quality Check: The individual segmentations (the process of outlining the hippocampus) were manually checked to ensure accuracy, with no boundary adjustments found necessary. Total hippocampal volume was calculated by summing the left and right volumes.

2. Verbal Memory and Learning (Secondary Outcome):

• Rey Auditory Verbal Learning Test (RAVLT): This is a widely used neuropsychological test to assess verbal learning and memory. Participants were read a list of 15 common words five times and asked to recall as many as possible after each reading. An "interference list" was then presented, followed by a recall of the original words. Finally, participants recalled the original words after a 20-minute delay.
• RAVLT Scores: Several scores were calculated from the RAVLT, including:
  • Total acquisition: The total number of words recalled across the five initial trials.
  • Recall after interference: Number of original words recalled after the interference list.
  • Loss after interference: The difference between words recalled on the fifth trial and words recalled after the interference list (a measure of susceptibility to new information).
  • Long delay free recall: Number of original words recalled after the 20-minute delay.
  • Recognition: Number of words correctly identified from a final list of 60 words.

3. Screening and Descriptive Measures:

• Mini-Mental State Examination (MMSE): A brief, 30-point questionnaire used to screen for cognitive impairment (score ≥ 24/30 for inclusion).
• **Montreal Cognitive Assessment (MoCA):